Blood NeoplasiaPub Date : 2024-03-01DOI: 10.1016/j.bneo.2024.100004
Ashwini Jambhekar , Emily E. Ackerman , Berk A. Alpay , Galit Lahav , Scott B. Lovitch
{"title":"Comparison of TP53 mutations in myelodysplasia and acute leukemia suggests divergent roles in initiation and progression","authors":"Ashwini Jambhekar , Emily E. Ackerman , Berk A. Alpay , Galit Lahav , Scott B. Lovitch","doi":"10.1016/j.bneo.2024.100004","DOIUrl":"https://doi.org/10.1016/j.bneo.2024.100004","url":null,"abstract":"<div><h3>Abstract</h3><p><em>TP53</em> mutation predicts adverse prognosis in many cancers, including myeloid neoplasms, but the mechanisms by which specific mutations affect disease biology, and whether they differ between disease categories, remain unknown. We analyzed <em>TP53</em> mutations in 4 myeloid neoplasm subtypes (myelodysplastic syndrome [MDS], acute myeloid leukemia [AML], AML with myelodysplasia-related changes [AML-MRC], and therapy-related AML), and identified differences in mutation types, spectrum, and hot spots between disease categories and in comparison to solid tumors. Missense mutations in the DNA-binding domain were most common across all categories, whereas inactivating mutations and mutations outside the DNA binding domain were more common in AML-MRC than in MDS. <em>TP53</em> mutations in MDS were more likely to retain transcriptional activity, and comutation profiles were distinct between disease categories and mutation types. Our findings suggest that mutated <em>TP53</em> contributes to initiation and progression of neoplasia via distinct mechanisms, and support the utility of specific identification of <em>TP53</em> mutations in myeloid malignancies.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 1","pages":"Article 100004"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000049/pdfft?md5=32a5eaf130b739b0f8a9549efb2c3a9f&pid=1-s2.0-S2950328024000049-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood NeoplasiaPub Date : 2024-03-01DOI: 10.1016/j.bneo.2024.100002
Saishravan Shyamsundar , Sheila K. Pierson , Caoilfhionn M. Connolly , Mayan Teles , Dorry L. Segev , William A. Werbel , Frits van Rhee , Corey Casper , Joshua D. Brandstadter , Ariela Noy , David C. Fajgenbaum
{"title":"Patients with Castleman disease report mild COVID-19 symptoms and mount a humoral response to SARS-CoV-2 vaccination","authors":"Saishravan Shyamsundar , Sheila K. Pierson , Caoilfhionn M. Connolly , Mayan Teles , Dorry L. Segev , William A. Werbel , Frits van Rhee , Corey Casper , Joshua D. Brandstadter , Ariela Noy , David C. Fajgenbaum","doi":"10.1016/j.bneo.2024.100002","DOIUrl":"10.1016/j.bneo.2024.100002","url":null,"abstract":"<div><h3>Abstract</h3><p>The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in increased morbidity and mortality in patients with impaired immunity, hematologic malignancies, and on immunosuppressive regimens. COVID-19 can cause a cytokine storm with some patients benefiting from blockade of the proinflammatory cytokine, interleukin 6 (IL-6). Because Castleman disease (CD) is an atypical lymphoproliferative disorder that can involve a cytokine storm and often requires immunosuppressive therapies, including IL-6 inhibition, we sought to evaluate outcomes after COVID-19 and SARS-CoV-2 vaccination in patients with CD. We administered a survey in April 2021 to characterize experiences with COVID-19 and SARS-CoV-2 vaccination among 300 patients enrolled in ACCELERATE, a CD natural history registry. Among 128 respondents, the prevalence of SARS-CoV-2 infection (16/95, 17%), severe disease (1/16, 6%), vaccination rates (112/128, 88%), and vaccine adverse effects after dose 1 (62/112, 55%) were comparable with that of the general US population. Although there were 2 cases of CD flares occurring shortly after SARS-CoV-2 infection (n = 1) and vaccination (n = 1), >100 patients that were infected and/or vaccinated did not experience CD flares. Among patients with CD, the median antispike titer 6 months after the second vaccine dose was comparable to that of individuals with other immune-related diseases and healthy populations. Despite being on immunosuppressive therapies, patients with CD do not appear to be at increased risk of poor COVID-19 outcomes and can mount a humoral response to SARS-CoV-2 vaccination. This study was registered at <span>www.ClinicalTrials.gov</span><svg><path></path></svg> as #NCT02817997.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 1","pages":"Article 100002"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000025/pdfft?md5=bf82a64a1d50dd31cc6c1c8b26e2de29&pid=1-s2.0-S2950328024000025-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139826118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"KIR3DL1-HLA-Bw status in CML is associated with achievement of TFR: the POKSTIC trial, a multicenter observational study","authors":"Hiroshi Ureshino , Yasunori Ueda , Shin Fujisawa , Kensuke Usuki , Hideo Tanaka , Masaya Okada , Shugo Kowata , Kazunori Murai , Asao Hirose , Motohiro Shindo , Takashi Kumagai , Tomoharu Takeoka , Kazuharu Kamachi , Keisuke Kidoguchi , Takero Shindo , Satoshi Iyama , Junki Inamura , Takafumi Nakao , Tsutomu Kobayashi , Eri Kawata , Shinya Kimura","doi":"10.1016/j.bneo.2024.100001","DOIUrl":"10.1016/j.bneo.2024.100001","url":null,"abstract":"<div><h3>Abstract</h3><p>Achievement of treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) discontinuation in patients who show a durable deep molecular response (DMR) during TKI treatment of chronic myeloid leukemia in chronic phase (CML-CP) is a therapeutic goal; however, the prognostic factors that predict successful achievement of TFR are unclear. Previously, we reported that killer immunoglobulin-like receptor (<em>KIR)</em> and <em>HLA</em> polymorphisms are associated with achievement of a DMR. Here, we investigated the association between <em>KIR</em> and <em>HLA</em> polymorphisms and TFR. We conducted the POKSTIC (POlymorphisms of Killer immunoglobulin-like receptor, which affect Stop Tyrosine kinase Inhibitor in patients with Chronic myeloid leukemia) trial, a multicenter collaborative observational study that enrolled 76 patients with CML-CP. The median age was 63 years (interquartile range [IQR], 49-70). Of 76 patients, 42 (56.6%; 95% confidence interval [CI], 47.7-66.8 at 6 months) discontinued TKIs without molecular relapse; the median follow-up time for TFR was 24 months (IQR, 16-64). <em>KIR</em> genotyping and allele typing did not identify risk factors for molecular relapse; however, univariate and multivariate analysis identified the combination of <em>KIR3DL1</em>-<em>HLA-Bw4</em> (an <em>HLA-B</em> allele) as an independent factor for a higher risk of molecular relapse (hazard ratio, 2.206; 95% CI, 1.112-4.376; <em>P</em> = .024). Notably, patients at higher risk of relapse had a significantly lower number of natural killer (NK) cells at TKI discontinuation than the other patients (CD16<sup>+</sup>/CD56<sup>+</sup> NK cells: median 499.63 cells per μL vs 629.17 cells per μL, respectively; <em>P</em> = .049). Thus, <em>KIR3DL1-HLA-Bw</em> status reflects NK cell responses and is associated with TFR. The study is registered with the UMIN Clinical Trials Registry as #UMIN000041798.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 1","pages":"Article 100001"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000013/pdfft?md5=4478bc59bb04e478596db505d5a8f1b4&pid=1-s2.0-S2950328024000013-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139819062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood NeoplasiaPub Date : 2024-03-01DOI: 10.1016/j.bneo.2024.100003
Benjamin A. Derman , Jacob Ambrose , Laura L. Fernandes , Christina M. Zettler , Eric Hansen , Andrew J. Belli , Ching-Kun Wang
{"title":"Real-world comparison of daratumumab-based regimens in relapsed/refractory multiple myeloma using health record data","authors":"Benjamin A. Derman , Jacob Ambrose , Laura L. Fernandes , Christina M. Zettler , Eric Hansen , Andrew J. Belli , Ching-Kun Wang","doi":"10.1016/j.bneo.2024.100003","DOIUrl":"10.1016/j.bneo.2024.100003","url":null,"abstract":"<div><h3>Abstract</h3><p>Daratumumab (dara)-based triplet therapies are commonly used in the second-line (2L) and third-line (3L) settings in relapsed/refractory multiple myeloma (RRMM), usually in combination with dexamethasone and either bortezomib (dara-Vd), carfilzomib (dara-Kd), or pomalidomide (dara-Pd). We performed a real-world (rw) analysis to directly compare these regimens, to our knowledge, for the first time. This was an observational, retrospective cohort study using COTA’s rw database of patients with MM who have initiated 2L or 3L therapy with dara-Vd, dara-Kd, or dara-Pd. rw time to next treatment (rwTTNT) and rw overall survival (rwOS) were analyzed using the Kaplan-Meier method. Comparative analyses were conducted using a trimmed inverse probability of treatment weighting method to control for potential confounders. A total of 639 patients received a dara-based regimen as either 2L or 3L therapy (dara-Vd, n = 201; dara-Kd, n = 122; and dara-Pd, n = 316). A high proportion had functional (52%) or cytogenetic (26%) high-risk disease; 49% were lenalidomide refractory. Median rwTTNT for dara-Vd was 7.6 months and was 12.9 months for dara-Kd (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.49-0.99). Similarly, median rwTTNT for dara-Vd was 6.9 months and 15.3 months for dara-Pd (HR, 0.57; 95% CI, 0.43-0.77). Median rwTTNT for dara-Pd was 15.7 months, and for dara-Kd 13.2 months (HR, 1.1; 95% CI, 0.8-1.6). No regimen was associated with superior rwOS. Among patients with RRMM receiving 2L or 3L therapy with a dara-based triplet, dara-Vd was associated with inferior rwTTNT compared with both dara-Kd and dara-Pd. dara-Vd may not be a suitable control arm for most phase 3 studies.</p></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"1 1","pages":"Article 100003"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950328024000037/pdfft?md5=d48c10ab1082c0948b3ca3433ec37ce2&pid=1-s2.0-S2950328024000037-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139873265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood NeoplasiaPub Date : 2024-02-01DOI: 10.1016/j.bneo.2024.100005
Hiroto Ohguchi, Yasuyo Ohguchi, Sho Kubota, Kan Etoh, Ai Hamashima, Shingo Usuki, Takako Yokomizo-Nakano, Jie Bai, Takeshi Masuda, Y. Kawano, Takeshi Harada, Mitsuyoshi Nakao, Takashi Minami, T. Hideshima, Kimi Araki, G. Sashida
{"title":"Multiple myeloma-associated DIS3 gene is essential for hematopoiesis but loss of DIS3 is insufficient for myelomagenesis","authors":"Hiroto Ohguchi, Yasuyo Ohguchi, Sho Kubota, Kan Etoh, Ai Hamashima, Shingo Usuki, Takako Yokomizo-Nakano, Jie Bai, Takeshi Masuda, Y. Kawano, Takeshi Harada, Mitsuyoshi Nakao, Takashi Minami, T. Hideshima, Kimi Araki, G. Sashida","doi":"10.1016/j.bneo.2024.100005","DOIUrl":"https://doi.org/10.1016/j.bneo.2024.100005","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"7 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139814612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood NeoplasiaPub Date : 2024-02-01DOI: 10.1016/j.bneo.2024.100002
S. Shyamsundar, S. Pierson, C. Connolly, M. Teles, D. Segev, W. Werbel, F. van Rhee, Corey Casper, Joshua D. Brandstadter, Ariela Noy, D. Fajgenbaum
{"title":"Castleman disease patients report mild COVID-19 symptoms and mount a humoral response to SARS-CoV-2 vaccination","authors":"S. Shyamsundar, S. Pierson, C. Connolly, M. Teles, D. Segev, W. Werbel, F. van Rhee, Corey Casper, Joshua D. Brandstadter, Ariela Noy, D. Fajgenbaum","doi":"10.1016/j.bneo.2024.100002","DOIUrl":"https://doi.org/10.1016/j.bneo.2024.100002","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"173 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139885906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood NeoplasiaPub Date : 2024-02-01DOI: 10.1016/j.bneo.2024.100006
Agnes Mattsson, J. Lundin, T. Mulder, S. E. Sylvan, M. Palma, L. Hansson, Anders Österborg
{"title":"Frequent response monitoring in chronic lymphocytic leukemia clinical trials: what is the value?","authors":"Agnes Mattsson, J. Lundin, T. Mulder, S. E. Sylvan, M. Palma, L. Hansson, Anders Österborg","doi":"10.1016/j.bneo.2024.100006","DOIUrl":"https://doi.org/10.1016/j.bneo.2024.100006","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"719 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139820587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood NeoplasiaPub Date : 2024-02-01DOI: 10.1016/j.bneo.2024.100003
B. Derman, J. Ambrose, L. Fernandes, C. Zettler, E. Hansen, A. Belli, Ching-Kun Wang
{"title":"Real-world Comparison of Daratumumab-Based Regimens in Relapsed/Refractory Multiple Myeloma Using Health Record Data","authors":"B. Derman, J. Ambrose, L. Fernandes, C. Zettler, E. Hansen, A. Belli, Ching-Kun Wang","doi":"10.1016/j.bneo.2024.100003","DOIUrl":"https://doi.org/10.1016/j.bneo.2024.100003","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139813452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}